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M Shimada

Publications and source records attributed to M Shimada.

At least 37 records · Page 2Linked to original sources
PubMed2001

Telomerase activity and p53-dependent apoptosis in ovarian cancer cells.

We conducted the present study to determine the relationship between p53-dependent apoptosis and telomerase activity in ovarian cancer cells. A human ovarian adenocarcinoma cell line, SK-OV-3 that had homozygous deletion of the p53 gene was used in this study. Wild-type p53 genes were transducted to SK-OV-3 cells with a recombinant adenovirus that contained a wild-type p53 gene (AxCAp53). IC(50)to cisplatin (CDDP) was 12.9 microM for SK-OV-3 cells and 9.2 microM for p53 gene-transducted SK-OV-3 cells. The apoptotic index for cells with p53 gene transduction was significantly higher than cells without transduction. Additionally, p53 gene transduction significantly enhanced CDDP-induced apoptosis. Bax protein in SK-OV-3 cells did not differ before and after exposure to CDDP. In SK-OV-3 cells with transduction of the p53 gene, the expression of p53 and Bax proteins increased after exposure to CDDP. Expression of Bcl-xL decreased after exposure to CDDP in SK-OV-3 cells with and without transduction. The telomerase activity in SK-OV-3 cells with the p53 gene was significantly lower compared with the cells without the p53 gene. CDDP exposure did not affect telomerase activity and human telomerase reverse transcriptase (hTERT) expression in both cell lines. We suggest that the p53 gene may relate to telomerase activity, but that p53-dependent apoptosis does not affect the activity.

Adenocarcinoma↗
PubMed2001

Laparoscopic hepatectomy for hepatocellular carcinoma.

BACKGROUND: No reports exist on the role of laparoscopic hepatectomy in the short- and long-term outcomes of patients with hepatocellular carcinoma (HCC). We present our results from using laparoscopic hepatectomy for HCC and discuss the importance of this procedure. METHODS: To investigate the role of laparoscopic hepatectomy in the short- and long-term outcomes, 17 patients with HCC who underwent laparoscopic hepatectomy (laparoscopic hepatectomy group) were compared with 38 patients who underwent conventional open hepatectomy (open hepatectomy group) during the same period. RESULTS: No differences in operation time, blood loss, rate of blood transfusion, or incidence of postoperative complications were found between the two groups. The postoperative hospital stay for the laparoscopic hepatectomy group was significantly shorter than for the open hepatectomy group. With long-term prognosis, no difference was found in survival rate and disease-free survival rate between the two groups. No recurrence was found in the stump of the remaining liver after laparoscopic hepatectomy. CONCLUSIONS: Laparoscopic hepatectomy has resulted in a better short-term outcome after surgery than conventional open hepatectomy. The long-term prognosis in the laparoscopic hepatectomy group was similar to that in the open hepatectomy group. Therefore, laparoscopic hepatectomy can be a new alternative for treatment of cirrhotic patients with HCC when patients are strictly selected.

Carcinoma, Hepatocellular↗
PubMed2001

Cytokine characteristics of jaundice in mouse liver.

OBJECTIVE: The aim of this study is to clarify the perioperative cytokine changes and their mechanism in jaundiced liver. MATERIALS AND METHODS: Obstructive jaundice was induced using a common bile duct ligation (CBDL) and a two-thirds hepatectomy (HEP) was performed in six- to seven-week-old male C3H/HeN mice. When hepatectomy was added to CBDL, it was carried out 2 to 5 days after CBDL. The serum interleukin 6 (IL-6) levels and heat shock protein (HSP)-70 expression were evaluated. One mg per mouse of methylprednisolone (MPL) was intraperitonealy administered in some mice of CBDL+HEP group. RESULTS: The post-hepatectomy IL-6 values at 2 and 3 days after CBDL were significantly lower than those in the HEP group, while those at 5 days after CBDL were significantly higher than those in HEP group. The serum IL-6 value of the steroid group was significantly lower than that of non-steroid group in HEP group. However, no steroid effects were recognized on post-hepatectomy IL-6 values at 3 days after CBDL, steroid inhibited post-hepatectomy IL-6 production at 5 days after CBDL. No expression of HSP70 protein was observed in the control group, but HSP70 protein was expressed in both the hepatocytes and Kupffer cells 3 days after CBDL, then at 5 days after CBDL, no HSP70 protein was expressed in the Kupffer cells. CONCLUSIONS: In the early period of obstructive jaundice, the IL-6 level after hepatectomy did not increase in comparison to HEP group, and steroid had no effect on IL-6 level. According to the progression of obstructive jaundice, the IL-6 level after hepatectomy increased to a higher level than before, and the effect of MPL was restored. HSP70 is thus suggested to have an important role in cytokine production.

Animals↗
PubMed2001

Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model.

Applications of nonviral vectors for gene transfer into tumors in vivo have been limited by the relatively low expression levels of the transferred gene. The aim of this study is to evaluate the efficacy of electroporation-mediated interleukin-12 (IL-12) gene therapy for hepatocellular carcinoma (HCC). First, we investigated the optimal conditions of electric pulses (voltage, pulsing duration, numbers of shocks) of in vivo electroporation for gene transfer into HCC established by s.c. implantation of MH134 cells to C3H mice. This process made use of plasmid DNA that express the luciferase gene. We concluded that the optimal conditions for the electric pulses are as follows: voltage at 150 V; pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of shocks at 10. Second, we tried to treat s.c. HCC by electroporation using plasmid DNA that expresses the murine interleukin-12 (mlL-12) gene. Intratumoral administration of the mIL-12 vector elevated serum IL-12 and IFN-gamma and significantly inhibited the growth not only of HCC into which the mIL-12 vector had been directly transferred, but also of the distant HCC. In addition, intratumoral administration of the mIL-12 vector inhibited spontaneous lung metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene therapy. The IL-12 gene therapy induced more lymphocyte infiltration by NK cells, CD3+ cells, and Mac-1 positive cells into the tumor and reduced the number of microvessels. Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive tumor cells were found. These results demonstrate that gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and is thus promising for further clinical trial.

Animals↗
PubMed2001

Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial.

HYPOTHESIS: Preoperative administration of methylprednisolone sodium succinate can control surgical stress in patients undergoing hepatic resection. DESIGN: A prospective randomized trial. SETTING: A university hospital department of surgery. PATIENTS: Thirty-three patients who underwent hepatic resection were classified into 2 groups: a control group (n = 16) and a steroid group (n = 17) in which patients were intravenously administered 500 mg of methylprednisolone 2 hours before surgery. MAIN OUTCOME MEASURES: Perioperative levels of interleukin (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein, Candida antigen, and other laboratory and clinical variables were measured. RESULTS: Postoperative levels of serum and peritoneal IL-6 and levels of C-reactive protein were significantly lower in the steroid group than in controls. Furthermore, serum and peritoneal IL-10 levels were significantly higher in the steroid group. The total bilirubin value on postoperative day 1 was significantly lower in the steroid group than in controls. Postoperative immunosuppressive acidic protein levels were also significantly lower in the steroid group, as was the positive rate of serum Candida antigen. No differences were found in the incidence of postoperative complications. CONCLUSIONS: Preoperative steroid administration significantly elevated anti-inflammatory cytokine IL-10 levels, suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and prevented postoperative elevation of total bilirubin values. Furthermore, postoperative elevation of immunosuppressive acidic protein levels and the positive rate of Candida antigen were suppressed, indicating that the immune response was maintained by preoperative steroid administration.

Acute-Phase Proteins↗
PubMed2001

Correlation of three-dimensional gradient echo dynamic MR imaging with CT during hepatic arteriography in patients with hypervascular hepatocellular carcinomas: preliminary clinical experience.

The purpose of this study is to elucidate the usefulness of dynamic MR study of the whole liver using 3DFISP with double dose gadolinium (Gd) enhancement in detecting enhancing lesions in 20 patients. Twenty patients with hepatocellular carcinoma (HCC) underwent 3DFISP dynamic study with double dose Gd. The demonstration of enhancing hypervascular lesions regardless of etiology was evaluated on a segment-by-segment basis with receiver operating characteristic (ROC) analysis, using findings on CT during hepatic arteriography as a gold standard. Diagnostic accuracy of 3DFISP in the detection of HCC was also evaluated. As to the demonstration of enhancing lesions, the Az value of the ROC curve was 88%. The detection rate of HCC with 3DFISP was 98%. 57% of enhancing pseudolesions were not detected on 3DFISP. We concluded that Dynamic MR study of the whole liver using 3DFISP with double dose Gd enhancement is a useful method to demonstrate hypervascular HCC.

Aged↗
PubMed2001

Depressive symptoms and associated factors in a cognitively normal elderly population: the Tajiri Project.

BACKGROUND AND OBJECTIVE: Since depression is one of the main problems of elderly subjects, it is important to examine the prevalence of this condition and to identify associated factors. METHODS: A total of 1525 cognitively normal subjects aged 65 years and over in the town of Tajiri, a typical agricultural town in Japan, were analysed. Their MMSE (mini-mental state examination) scores were 24 or over. Depressive state was assessed by Zung's SDS (self-rating depression scale) with a comprehensive interview to examine ADL, demographics and symptoms associated with illness, etc. The prevalence of depression was calculated. To determine the factors associated with depression, the t-test and the Chi-square test were used. To examine the relative strength of each factor, logistic regression analysis was performed. RESULTS: The ratio of the depressive subjects was 6.4%, lower than those of previous reports, probably due to the effect of excluding dementia subjects. The ratio for older females aged 80 years and over was 14.3%, which was significantly higher than that of the males. Among socio-demographic factors, sex, age, number of children and perception of economic status, were significantly related. For health status and ADL, such factors as perception of health and medical history of heart disease and rheumatism were related. For familial and social status, factors such as daily activity and several conversation abilities were related. The logistic regression analysis indicated that perception of health and daily activity were associated. CONCLUSIONS: In this study, we isolated some factors related to depression in a cognitively normal population. Knowledge of such factors is important for appropriate mental care of aged subjects.

Activities of Daily Living↗
PubMed2001

Neuronal apoptosis mediated by IL-1 beta expression in viral encephalitis caused by a neuroadapted strain of the mumps virus (Kilham Strain) in hamsters.

The neuroadapted Kilham strain of the mumps virus produces lethal encephalitis in newborn hamsters after intracerebral inoculation. The pathogenesis of this encephalitis is not fully understood, but recently, apoptosis and associated cytokine production have been recognized to be major pathologic mechanisms by which viruses cause injury to neuronal host cells. To analyze the main factors producing brain injury in this viral encephalitis, the following questions were investigated: (1) does the virus induce neuronal apoptosis and (2) does expression of cytokines regulate the induction of neuronal apoptosis? Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used as a marker of neuronal apoptosis and TUNEL-positive neurons were widespread in the infected cerebral cortex. DNA fragmentation yielding DNA ladders characteristic of apoptosis was also observed in infected hamster brain tissue. Apoptotic cells in infected brains were observed after the appearance of inflammatory changes. Overexpression of IL-1 beta, but not TNF-alpha or Fas-L, was clearly detected in infected brains, as determined by Western blot and RT-PCR. Immunohistochemistry revealed a striking correlation between IL-1 beta expression and neuronal apoptosis. Injection of recombinant IL-1 beta into normal hamster brain resulted in neuronal apoptosis in cerebral cortex. On the other hand, neutralizing IL-1 beta antibodies decreased the number of cells undergoing apoptosis in infected hamster brains and subsequent death. We conclude that the fatal encephalitis induced by the Kilham strain of the mumps virus is mediated by immunopathological processes and that overexpression of IL-1 beta, which mediates the induction of neuronal apoptosis, may play a major role in these processes.

Animals↗
PubMed2001

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus.

OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS: Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.

Aged↗
PubMed2001

Characteristics of multicentric hepatocellular carcinomas: comparison with intrahepatic metastasis.

Characteristics of multicentric hepatocellular carcinomas (HCCs) remain obscure. We therefore aimed to clarify them and compare them with HCC with intrahepatic metastases. A series of 118 patients who had definite hepatitis C viral status and multinodular HCC were divided into two groups: a multicentric occurrence (MO) group (n = 38), with multicentric HCCs; and an intrahepatic metastasis (IM) group (n = 80), with HCC having intrahepatic metastases. Clinicopathologic variables, including the patient's survival and disease-free survival rates, were compared between the MO and IM groups. Univariate analysis revealed the presence of esophageal varices, the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, hepaplastin test, gamma-globulin, the histologically active hepatitis, tumor size, des-gamma-carboxy prothrombin > 0.1 AU/ml, positive portal vein invasion, and histologic grade as discriminating factors. The MO score to differentiate multicentric HCCs from intrahepatic metastatic HCCs was determined using the following four independent factors selected by a stepwise regression analysis: the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, tumor size, and histologic grade. The sensitivity and specificity of the MO scores using those factors were 84% and 70%, respectively, when the cutoff value was 0.4. The disease-free survival rate in the MO group was similar to that in the IM group, whereas the survival rate in the MO group was significantly better than that in the IM group. The multivariate analysis revealed the multicentric occurrence of HCC as one of the independent prognostic factors. Clinicopathologic factors differentiating multicentric HCCs from intrahepatic metastatic HCCs were the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, small tumor size, and low histologic grade.

Carcinoma, Hepatocellular↗
PubMed2001

Techniques available for the management of massive sacrococcygeal teratomas.

An infant born in the 34th week of gestation weighing 5,355 g with a massive sacrococcygeal (SC) tumor was delivered by elective cesarean section. An ultrasonographic examination showed solid and cystic components in the tumor. Resection was successfully undertaken with insertion of a Nélaton catheter into the rectum to avoid unnecessary impairment of the viscera. The tumor weighed 2,380 g, measured 25 x 14 x 11 cm, and was clinicopathologically diagnosed to be a SC teratoma. This experience and other publications show that several considerations including control of hemorrhage and coagulopathies, visceral protection, and avoidance of wound infection are necessary to facilitate the surgical management of massive SC tumors. Several suggestions are made concerning the pre- and intraoperative management of this rare tumor.

Female↗
PubMed2001

Repeat hepatectomy is the most useful treatment for recurrent hepatocellular carcinoma.

Hepatic resection has been regarded as a curative treatment for primary hepatocellular carcinoma (HCC), but a high incidence of postoperative recurrence is general. Thus it is important to predict the patterns of recurrence and select the appropriate treatment for recurrence for a better long-term prognosis of patients with HCC. Clinicopathological studies on 80 patients with intrahepatic recurrence after curative hepatectomy suggested that nodular-type recurrence with up to three nodules is mainly due to metachronous multicentric hepatocarcinogenesis rather than intrahepatic metastases. We reviewed 300 patients with recurrent HCC, and repeat hepatectomy was done in 78 cases (26.0%). The 3- and 5-year survival rates after repeat hepatectomy were 82.8% and 47.5%, respectively, showing better prognosis than those for other treatments. Repeat hepatectomy is the preferred treatment offering a hope of long-term survival for patients with recurrent HCC as long as liver function is sufficient; thus early detection of recurrence should be ensured.

Adult↗
PubMed2001

The role of macroscopic classification in nodular-type hepatocellular carcinoma.

BACKGROUND: Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. METHODS: Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. RESULTS: The alpha-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. CONCLUSIONS: Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.

Carcinoma, Hepatocellular↗
PubMed2001

The role of overexpression and gene amplification of cyclin D1 in intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignant tumor with an extremely poor prognosis, but less attention has been directed to factors related to molecular carcinogenesis, including cell cycle proteins. We examined the expression and gene amplification of cyclin D1, the cell cycle regulating protein. Our objective was to evaluate correlations with clinicopathological factors in ICC. METHODS: Cyclin D1 overexpression and cellular proliferative activity (Ki-67 labeling index) were investigated immunohistochemically, and 20 cases were further investigated for cyclin D1 gene amplification, using differential PCR. We examined the correlation between the expression and gene amplification of cyclin D1 and clinicopathological factors, including overall survival in patients with ICC. RESULTS: Immunohistochemical analysis revealed an overexpression of cyclin D1 protein in 28 of 66 subjects with ICCs (42%). The cyclin D1 overexpression was associated with poor histological differentiation (P = 0.04), high cellular proliferative activity (P < 0.01), and a poor prognosis (P = 0.02) by univariate analysis, although it is not an independent prognostic factor by multivariate analysis. Cyclin D1 gene amplification was confirmed in five of the 20 patients. Of those five cases of ICC, all had poor histological differentiation, and four of the five ICCs (80%) showed evidence of cyclin D1 immunoreactivity. CONCLUSIONS: Overexpression and gene amplification of cyclin D1 are frequent and contribute to dedifferentiation and cellular proliferative activity of ICCs, and overexpression also indicates a poor prognosis for patients with ICC.

Adult↗
PubMed2001

Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection.

BACKGROUND/AIMS: To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. METHODS: To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. RESULTS: Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. CONCLUSIONS: The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.

Adult↗
PubMed2001

Altered expression of beta-catenin without genetic mutation in intrahepatic cholangiocarcinoma.

beta-catenin which has a role in E-cadherin mediated cell-to-cell adhesion, and is also involved in Wnt signaling pathways as a downstream signaling molecule accumulating in the cytoplasm and nucleus constitutively activates Tcf/LEF-associated transcription of oncogenic genes. We examined the expression pattern and the genetic alteration of beta-catenin to determine the role of beta-catenin in cancer formation and/or progression in intrahepatic cholangiocarcinoma (ICC). beta-catenin expression was immunohistochemically examined in 71 surgically resected ICC samples, and correlation between the expression pattern and clinicopathologic factors was investigated. Mutation analysis of beta-catenin exon 3, which included the responsible element for Wnt signaling was done in 55 samples, using PCR-SSCP and direct sequence methods. Immunohistochemical analysis revealed the reduced membranous expression of beta-catenin in 58 (82%) ICCs and aberrant nuclear expression in 11 (15%) ICCs. The membranous expression was preserved in 62% of the papillary adenocarcinomas, and was frequently reduced in tumors with a poorer histological differentiation (84%), with a significant difference (P =.01). Genetic analysis showed that none of the 55 ICCs examined carried mutations in beta-catenin exon 3. The present study indicates that reduced membranous expression of beta-catenin is associated with non-papillary ICCs which have a more malignant behavior, and that nuclear translocation of beta-catenin results in oncogenic events. Mutations in beta-catenin exon 3 do not appear to be responsible for nuclear translocation of beta-catenin in ICCs.

Aged↗